An inspiration-off attractor supports the robust and flexible control of breathing

Abstract

Breathing is a fundamental motor rhythm necessary to sustain life. The rhythm and pattern of breathing arises from the coordination of a bilaterally symmetric, rostro-caudally extended column of heterogeneous neural populations in the medulla called the Ventral Respiratory Column (VRC). By recording from the extent of the VRC using Neuropixels during optogenetic and physiological manipulations, and projecting the population activity into a dynamical latent space, we find that GABAergic lung-stretch feedback circuits promote rhythmic population activity by creating a temporary stable fixed point in the latent state that terminates diaphragmatic contraction. Stimulation of GABAergic circuits either intrinsic to the VRC (VRCGABA) or via afferent pathways from GABAergic neurons of the Nucleus of the Solitary Tract (NTSGABA) advance or delay breathing when activated with specific respiratory phase through temporary stabilization of this fixed point. Lastly, we show that activation of glutamatergic signaling opposes the effects of inhibitory signaling by destabilizing this expiratory fixed point to promote rapid inspiration. Together, we decompose the functional impact of different respiratory control subpopulations to reveal an integrated network level mechanism for respiratory control in vivo.